1. Field of the Invention
The present invention relates to microfluidic devices and assay methods for selecting and optimizing the delivery of drugs across the blood-brain barrier.
2. Description of Related Art
Screening drug candidates and drug delivery vehicles for their abilities to cross from the blood into the brain through the Blood-Brain Barrier (BBB) is an important aspect of the development of Central Nervous System (CNS) therapeutics. Available in vitro BBB assays use incubation chambers separated by a filter membrane designed to mimic the BBB. Such devices do not reproduce physiological microenvironmental parameters, shear stress induced by blood flow and transport effects caused by phenotypic changes in the microvasculature. In vivo BBB assays involve small animal models that are expensive, lengthy and difficult to scale up for high throughput screening. Existing in vitro and in vitro BBB assays do not provide cost- and time-effective formats for real-time visualization or quantitation of the transport of drug and drug delivery candidates across the BBB.
The Synthetic Microvascular Blood-Brain Barrier (SyM-BBB) provides apparatus and methods for predicting drug and drug carrier transport across the BBB. In addition, it can be used to study dysfunction of the BBB following an insult (biological, chemical, mechanical or electrical). Interactions of cells under normal and pathological conditions with the BBB can also be visualized and quantitated in real-time.
Compared with static well-plate incubation assays as well as the other available in vitro platforms, the SyM-BBB accurately reproduces in vivo size and flow microenvironments and enables a physiologically-relevant testing system for drug screening and delivery experiments, as well as basic and applied research. Polymeric microfluidic technology (polydimethylsiloxane or PDMS) is used to create inexpensive, disposable chips. PDMS constructs can be used to realize long-term cell culture and cellular assays on these microfluidic chips. By bonding the polymer microchannel onto a custom glass bottom laid out in the appropriate form, the model also be readily extended onto standard 24 or 96 well plates, providing a ready method to scale up to high-throughput screening.